In 1978, an antisense oligonucleotide (antisense molecule) was first reported to have inhibited influenza virus infection. Thereafter, it has also been reported to have inhibited expression of cancer gene and AIDS infection. Since antisense oligonucleotide specifically regulates expression of undesirable genes, the field thereof is one of the most expected fields in recent years as a target of a pharmaceutical product development.
However, when natural DNA or RNA oligonucleotide is applied as an antisense molecule to this method, many problems occur such as hydrolysis by enzymes in the body, not high cellular membrane permeability and the like. To solve such problems, many nucleic acid derivatives have been synthesized, and the properties thereof have been studied. For example, phosphorothioates wherein an oxygen atom on the phosphorus atom of nucleic acid is substituted by a sulfur atom, and methylphosphonates wherein an oxygen atom on the phosphorus atom of nucleic acid is substituted by a methyl group have been synthesized, and recently, a molecule wherein a phosphorus atom is also substituted by a carbon atom, and a molecule wherein ribose is modified to an acyclic skeleton have also been synthesized.
Recently, it has been reported that a DNA or RNA oligonucleotide containing an artificial nucleic acid 2′,4′BNANC unit represented by the formula
wherein each symbol is as defined in patent document 1, and the carbon atom at the 2-position and the carbon atom at the 4-position of the sugar moiety in the nucleoside molecule are NO-bridged (in the present specification, such compound is sometimes generically referred to as “NC type nucleoside”) is a highly useful oligonucleotide derivative, since it shows a very high ability to form a double strand of complementary RNA chain, is superior in nuclease resistance, and permits binding of various other functional molecules to the NO bond (see patent document 1).
Non-patent document 1 discloses production methods of 2′,4′-BNACOC units having a purine nucleobase (to be referred to as “COC type (purine) nucleoside” in the present specification).
Non-patent document 2 discloses a glycosylation reaction using a silylated purine nucleobase.
Non-patent document 3 discloses synthetic methods of amino LNA purine derivatives.
Non-patent document 4 discloses synthetic methods of 2′-amino-2′-deoxynucleoside purine derivatives.
Non-patent document 5 and patent document 2 disclose synthetic methods of 2′-O-Me-nucleosidepurine derivatives.
However, none of the above-mentioned documents disclose a method of directly synthesizing an NC type purine nucleoside from an NC type pyrimidine nucleoside.